This proposal outlines a program directed at the discovery and development of an efficient catalytic method for the enantioselective conjugate addition of water to alpha,beta-unsaturated carbonyl systems. Catalyst development will be carried out in aqueous media and will be based on thorough and mechanism driven investigations into the bifunctional nature of the Schiff base dipeptide catalysts of Hoveyda and Snapper. Catalysts discovered for the enantioselective conjugate addition of water will provide systems that have the potential to be optimized toward other C-0 bond forming reactions of critical importance to asymmetric synthesis. We will therefore systematically optimize these catalysts toward the enantioselective synthesis of tetrahydrofuranyl and tetrahydropyranyl-based chiral synthons via an asymmetric intramolecular oxa-Michael addition protocol. We will showcase the utility of this methodology by demonstrating, for the first time, the total synthesis of iridoid related polyketide buergerinin F, where the requisite functionality and accompanying stereocenters are created in a de novo fashion.